The present invention relates to a thiazolidinedione derivative, represented in formula (1) below, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof. Further, the present invention provides a pharmaceutical composition comprising the compound represented in formula (1) below. 
wherein:
X represents a carbon or nitrogen atom; Y represents a hydrogen atom, an alkyl group, an alkoxy group, a halogen, or an aryl group; Z represents an oxygen, nitrogen, or sulfur atom; and R1 and R2 each represent a hydrogen atom, or R1 and R2 together form a bond.
Thiazolidinedione based compounds are oral diabetes therapeutic agents for treating insulin resistance, using a new mechanism different from that of conventional diabetes therapeutic agents. They lower blood sugar level by increasing physiological effects of insulin on target cells (muscle, adipocytes, liver, etc.). Now, the thiazolidinedione based compounds are highlighted as new diabetes therapeutic agents. Further, it has been reported in several documents that as insulin, free fatty acid, and triglyceride, etc. accumulate to high levels in the body, the thiazolidinedione based compounds strongly suppress further synthesis (Miuoru Oguchi, et al., J.Med. Chem., 2000, 43, 3052-3066; B. B. Lohray, et al., J. Med. Chem., 1999, 42, 2569-2581; Braj. B. Lohray, V. Bhushan, et al., Bioorg. Med. Chem. Lett., 1997, 7(7), 785-788; Kelving. Liu, et al., Bioorg. Med. Chem. Lett., 2001, 11, 2385-2388; T. M. Willson et al., J. Med. Chem., 2000, 43(4), 527-550; Jeffery, E. Cobb, et al., J. Med. Chem., 1996, 39, 665-668; J. Med. Chem., 1998, 41, 5055-5069; John L. Collins, et al., J. Med. Chem., 1998, 41, 5037-5054; Hisashi Shinkai et al., J. Med. Chem., 1998, 41, 1927-1933).
Rosiglitazone is commercially available. It is the strongest thiazolidinedione based compound discovered until now. It has been disclosed in European Patent Laid-Open Publication No. 0,842,925 and a journal (J. Med. Chem., 1994, 37, 3977-3985), which are incorporated herein by reference.
Rosiglitazone, having a structure similar to that of the present invention, is represented in formula (2) below. 
wherein, A1 is formula (a) or (b) below: 
wherein, R4 and R5 each independently represent a hydrogen atom, an alkyl group or a substituted or unsubstituted aryl group, or when R4 and R5 are each attached to adjacent carbons, R4 and R5 together with the carbon atoms to which they are attached form a benzene ring, in which each carbon atom represented by R4 and R5 together may be substituted or unsubstituted.
Rosiglitazone exhibits a moderate blood sugar-lowering effect, but has little activity versus hyperlipidemia, which is common in patients with diabetes. Furthermore, because its half life is short in terms of pharmacodynamics, it must be inconveniently administered twice a day. In rare cases, it has been clinically reported that liver toxicity involved in use of rosiglitazone drugs causes death. Therefore, there is a disadvantage in that the patients with diabetes must have their liver function tested periodically.
Therefore, the present invention has been made in view of the above problems, and it is an object of the present invention to provide a new thiazolidinedione based compound having activities such as strong blood sugar lowering action and strong blood lipid lowering action, compared with rosiglitazone, and a pharmaceutical composition containing the thiazolidinedione based compound.
It is another object of the present invention to provide a new thiazolidinedione based compound, in which its half-life is remarkably prolonged, and a pharmaceutical composition containing the thiazolidinedione based compound.
It is yet another object of the present invention to provide a new thiazolidinedione based compound, in which liver toxicity, a common side effect encountered with this type of compound drug, is not found, and a pharmaceutical composition containing the thiazolidinedione based compound.